Positron emission tomography (PET) studies have shown abnormalities in glucose use rates and blood flow in certain brain regions, such as the anterior cingulate and the amygdala/hippocampus complex, of subjects with mood disorders, such as depression, seem to normalize in response to antidepressant treatment. For instance, magnetic resonance spectroscopy (1H MRS) studies have shown abnormalities of energy-intensive cellular membrane phospholipid metabolism, as measured by altered choline/creatine ratios, in the orbitofrontal cortex of depressed subjects. Observations of altered brain 1H MRS choline levels in depressed patients appear to be consistent with altered brain energy metabolism.
A limited number of studies have addressed changes in brain energy metabolism as measured by phosphorus (31P) MRS in MDD subjects. This literature describes certain abnormalities in bioenergetic metabolism, primarily a decreased baseline level of β-nucleoside triphosphate (β-NTP) and total NTP in the basal ganglia and the frontal lobes of MDD subjects as compared to normal control subjects. Previous studies do not reliably indicate whether brain bioenergetic abnormalities in MDD represent a biological trait of subjects at risk for MDD or whether subjects at risk for MDD are dependent on the state and severity of depression.
Thyroid hormones, especially triiodothyronine (T3), have been shown effective as an augmentation strategy in treatment resistant depression (TRD). Data from previously published reports support their role for augmentation of tricyclic antidepressant drugs, and some studies have indicated a moderate efficacy of thyroid hormones as adjuvants to selective serotonin reuptake inhibitors (SSRI) in TRD.